Sterilization of intraocular lenses

ABSTRACT

A packaged, sterilized intraocular lens prepared by a process comprising providing a hydrophobic acrylic, or low water acrylic, intraocular lens and positioning the acrylic lens in a lens enclosure with an aqueous solution to provide a lens package. The lens package is then heated to a temperature sufficient for sterilization, however, the heating of the lens package must begin before the acrylic lens reaches an equilibrated, hydrated state following contact of the lens with the aqueous solution. The resulting sterilized acrylic intraocular lens will have less than sixty percent of total volume of disc-like features, or less than forty percent of total volume of water vacuoles, after 60 days following sterilization compared to an acrylic lens of the same composition, which was sterilized under the same conditions, but in an equilibrated, hydrated state.

CROSS REFERENCE

This application claims the benefit of Provisional Patent ApplicationNo. 61/146,445 filed Jan. 22, 2009, which is incorporated by referenceherein.

FIELD OF THE INVENTION

The invention relates to intraocular lenses (IOLs) and methods ofsterilizing IOLs. In particular, the invention relates to hydrophobic,acrylic IOLs or low water content, acrylic IOLs and methods ofsterilizing such IOLs.

BACKGROUND OF THE INVENTION

Since the 1940s IOLs have been utilized as replacements for diseased ordamaged natural ocular lenses. In most cases, an IOL is implanted withinan eye at the time of surgically removing the diseased or damagednatural lens, such as for example, in the case of cataracts. Fordecades, the preferred material for fabricating IOLs was poly(methylmethacrylate), which is a rigid, glassy polymer.

As the technology in IOL materials progressed, softer, more flexibleIOLs have gained acceptance because of their ability to be compressed,folded, rolled or otherwise deformed. As a result, the IOLs can bedeformed prior to insertion of the lens through an incision in thecornea and into the eye. Once inserted, the IOL is carefully unfolded bythe surgeon and the lens returns to its original pre-deformed shape.These softer IOLs can be inserted into an incision of less than 3.0 mm,whereas the earlier, more rigid IOLs required an incision size of 5 to7.0 mm, i.e., an incision size slightly larger than the diameter of theoptic portion of the IOL. Since larger incisions lead to an increasedincidence of postoperative complications, the softer, more flexible IOLsare typically preferred by ocular surgeons.

The refractive power of a lens is a function of its shape and therefractive index of the material of which it is made. Accordingly, alens made from a material having a higher refractive index can bethinner and provide the same refractive power as a lens made from amaterial having a relatively lower refractive index. For IOLs designedto be rolled or folded for insertion through a small incision, a lens ofthinner cross section is inherently more flexible and can be rolled orfolded to a smaller cross section.

In general, the materials of current commercial IOLs fall into one ofthree general categories: silicones, low-water hydrophilic acrylics andhydrophobic acrylics. Hydrophobic acrylic materials with a relativelylow glass transition temperature (Tg ° C.) possess important materialcharacteristics—they typically have a high refractive index and unfoldwith a greater degree of control. Low Tg, hydrophobic acrylic materialscontain little or no water at the point of manufacture, however they doabsorb small amounts of water over time if stored in an aqueous mediumor following ocular insertion. The absorbed water often leads to pocketsof water or vacuoles within the polymeric matrix, which leads to areduction in the visual quality of the lens. Low Tg, hydrophobic acrylicmaterials also are known to develop disc-like features, which also leadto a reduction in the visual quality of the lens. The use of low water,hydrophilic acrylics minimizes the formation of these disc-like featuresand vacuoles.

Accordingly, there is an interest to develop a manufacturing processthat minimizes the formation of the disc-like features and vacuoles inhydrophobic acrylic and low water, hydrophilic acrylic IOLs.

SUMMARY OF THE INVENTION

The invention is directed to a packaged, sterilized intraocular lensprepared by a process comprising providing a hydrophobic acrylic, or lowwater acrylic, intraocular lens and positioning the acrylic lens in alens enclosure with an aqueous solution to provide a lens package. Thelens package is then heated to a temperature sufficient forsterilization, however, the heating of the lens package must beginbefore the acrylic lens reaches an equilibrated, hydrated statefollowing contact of the lens with the aqueous solution. The resultingsterilized acrylic intraocular lens will have less than sixty percent oftotal volume of disc-like features after 60 days following sterilizationcompared to an acrylic lens of the same composition, which wassterilized under the same conditions, but in an equilibrated, hydratedstate.

The invention is also directed to a packaged, sterilized intraocularlens prepared by a process comprising providing a hydrophobic acrylic,or low water acrylic, intraocular lens and positioning the acrylic lensin a lens enclosure with an aqueous solution to provide a lens package.The lens package is then heated to a temperature sufficient forsterilization, however, the heating of the lens package must beginbefore the acrylic lens reaches an equilibrated, hydrated statefollowing contact of the lens with the aqueous solution. The resultingsterilized acrylic intraocular lens will have less than forty percent oftotal volume of water vacuoles after 60 days following sterilizationcompared to an acrylic lens of the same composition, which wassterilized under the same conditions, but in an equilibrated, hydratedstate.

DETAILED DESCRIPTION OF THE INVENTION

The described process for hydrophobic acrylic, or low water acrylic,intraocular lenses (IOLs) minimizes the total volume of disc-likefeatures that are observed over time, that is, at 60 days followingsterilization in an aqueous solution. One of ordinary skill in the artwould recognize the disc-like features as “Frisbee-like” discs ofvarying size and orientation distributed throughout the acrylic lensmaterial. The formation of the unwanted disc-like features leads to areduction in visual quality of the lens.

The term “disc-like features” is recognized by one of ordinary skill inthe art of developing polymeric, optical materials as those visiblefeatures that develop in some optical materials, particularly,hydrophobic acrylic materials, following a heat treatment, e.g.,sterilization, in an aqueous environment. The disc-like features, whichtend to be randomly distributed throughout the material, are visible tothe eye with a microscope. Without being limited to a particular theory,Applicants suspect that the disc-like features are the result of a phasetransition in the material caused by the stress of the heat treatmentand the aqueous environment.

Applicants have developed a specific sterilization process to minimizethe formation of disc-like features in sterilized hydrophobic acrylic,or low water acrylic, IOLs. In nearly every processing lot the describedsterilization process provided sterilized IOLs with less than sixtypercent, and in many cases less than thirty percent, and in most casesless than ten percent, of total volume of disc-like features after 60days following sterilization compared to an acrylic IOL of the samecomposition that was sterilized under the same conditions, but in anequilibrated, hydrated form. In fact, in nearly all of the studiesconducted to date, the described and claimed sterilization processcompletely eliminated the formation of discostic stress features insterilized hydrophobic acrylic, or low water acrylic, IOLs. Moreover,the acrylic lenses remain free of the disc-like features indefinitely.

The described process for hydrophobic acrylic, or low water acrylic,intraocular lenses (IOLs) also minimizes the total volume of watervacuoles that are observed over time, that is, at 60 days followingsterilization in an aqueous solution. One of ordinary skill in the artwould recognize the water vacuoles as micro-bubbles of varying sizedistributed throughout the hydrophobic acrylic lens material. Applicantsbelieve that the water vacuoles form as small amounts of water becomeentrapped within the lens material. To reduce the degree of surfacetension between the aqueous water interface and the hydrophobic materialmicro-bubbles form. The formation of the unwanted water vacuoles leadsto a reduction in visual quality of the lens.

Applicants' sterilization process minimizes the formation of watervacuoles in sterilized hydrophobic acrylic, or low water acrylic, IOLs.In nearly every processing lot the described sterilization processprovided sterilized IOLs with less than forty percent, and in most casesless than thirty percent, of total volume of water vacuoles 60 daysfollowing sterilization compared to an acrylic IOL of the samecomposition that was sterilized under the same conditions, but in anequilibrated, hydrated form.

Accordingly, the invention is directed to a sterilized intraocular lensprepared by a process comprising providing a hydrophobic acrylic, or lowwater content acrylic, intraocular lens and positioning the acrylic lensin a lens enclosure with an aqueous solution to provide a lens package.The lens package is then heated to a temperature sufficient forsterilization, however, the heating of the lens package must beginbefore the acrylic lens reaches an equilibrated, hydrated statefollowing contact of the lens with the aqueous solution. The resultingsterilized intraocular lens will have less than sixty percent,preferably less than thirty percent, more preferably less than tenpercent, total volume of discotic features, or less than forty percent,and in most cases less than thirty percent, of total volume of watervacuoles, 60 days following sterilization than a lens of the samecomposition that was sterilized under the same conditions, but in anequilibrated, hydrated state.

As described in greater detail, the IOLs sterilized by the describedprocedure are only those characterized by those of ordinary skill in theart as hydrophobic acrylic, or low water content acrylic, IOLs. The term“hydrophobic acrylic” means that in an equilibrated, hydrated state thelens will comprise less than 10% by weight water. See, polymeric lensmaterials described under the sub-heading, “Hydrophobic Acrylic IOLs”.In one embodiment, the hydrophobic acrylic intraocular lens sterilizedby the described process can include silicon monomeric units. See,polymeric lens materials described under the sub-heading, “HydrophobicSilicone IOLs”.

The term “low water content acrylic” is a (meth)acrylate material thatin an equilibrated, hydrated state the lens will comprise from 5% to 15%by weight water. See, polymeric lens materials described under thesub-heading, “Low Water Content Acrylic IOLs”.

One of ordinary skill in the art would understand that the term“equilibrated hydrated state” means that a lens in contact with anaqueous solution is allowed sufficient time for the water to becomeabsorbed into the lens and reach a state of equilibrium such that thelens is not capable of absorbing additional amounts of water from thesolution. The time it takes for any one hydrophobic lens to reach anequilibrated hydrated state is determined by carefully weighing the lensdisposed in the solution at different time intervals and recording thetime it takes for the lens to reach a substantially constant weight.

In one embodiment, the heating of the lens for sterilization beginsbefore the lens reaches a 50% hydrated state, that is, the lens hasabsorbed less than 50% by weight of the water for a given aqueoussolution compared to the total amount of water the lens would absorbusing the same aqueous solution but allowing the lens to reach itsequilibrated hydrated state. Similarly, in another embodiment, theheating of the lens for sterilization begins before the lens reaches a25% hydrated state.

In one embodiment, the heating of the lens package begins within sixhours of contacting the lens with the aqueous solution with the lenspackage at room temperature. In another embodiment, the heating of thelens package should begin within two hours of contacting the lens withthe aqueous solution with the lens package at room temperature.

Typically, an intraocular lens is manufactured in one of two ways. Onemethod involves casting the IOL in a lens mold of set dimensions toprovide a lens with a predetermined optical power. The lens is thenremoved from the mold and extracted with water, an organic solvent or amixed aqueous organic solvent, e.g., water/hexanol, to remove reactionside products, e.g., oligomers, or unreacted monomer. The lens canfurther be refined, e.g., edging or polishing the lens within setquality specifications. The refined lens is then placed in a bufferedsaline solution and the lens material reaches an equilibrated hydratedstate prior to sterilization. The sterilization process will generallyinclude the sealing of the lens package prior to sterilization.

The second method involves casting the polymeric material in the form ofa rod. The rod is sliced to provide polymeric discs or “buttons”, whichare then machined to the desired shaped IOL. The buttons or machined IOLis then extracted to remove reaction impurities. Again, the refined lensis placed in the buffered saline solution and the lens material reachesan equilibrated hydrated state prior to sterilization.

As stated, each of the above manufacturing methods will often include anextraction step. Accordingly, the described process can includeextracting a polymerized hydrophobic intraocular lens with alow-expanding organic solvent to remove unwanted polymerization productsor non-reacted monomer from the polymerized lens.

Following the extraction process, the hydrophobic IOL is preferably notplaced in buffered saline, but is instead, dried under vacuum attemperatures from 40° C. to 110° C. for at least thirty minutes. The IOLis maintained in a dry state until the sterilization process.

It is to be understood, however, that one of ordinary skill in the artof developing or manufacturing optical polymeric lenses understands thatan extraction step is optional, and materials and processes can bedeveloped that would exclude such an extraction step.

Hydrophobic Acrylic IOLs

Hydrophobic acrylic IOLs are essentially a copolymer comprised of atleast three monomeric components. The first monomeric component, whichis preferably present in the copolymer from about 30% to about 85% byweight, is best described by its corresponding homopolymer. Thehomopolymer of the first monomeric component will have a refractiveindex of at least about 1.50, preferably at least about 1.52 or about1.54, and preferably have a substantial degree of rigidity. Likewise,the second monomeric component, which is preferably present in thecopolymer from 5% to about 30% by weight, is best described by itscorresponding homopolymer. The homopolymer of the second monomericcomponent will have a glass transition temperature from about −100° C.to about 60° C. The first and second monomeric components preferablyconstitute at least about 80%, more preferably at least about 90%, byweight of the copolymer. Moreover, it can be advantages to use a firstand a second monomeric components that have similar reactivity ratiossuch that a more homogeneous copolymer matrix is prepared from the twomonomeric components.

As used herein, the term “homopolymer” refers to a polymer which isderived substantially completely from the monomeric component inquestion. Thus, such homopolymer includes as the primary, preferablysole, monomeric component, the monomeric component in question. Minoramounts of catalysts, initiators and the like can be included, as isconventionally the case, in order to facilitate the formation of thehomopolymer.

The third monomeric component of the copolymer is a crosslinkingcomponent, which can form crosslinks with each of the first and secondmonomeric components. The crosslinking monomeric component is preferablymultifunctional and can chemically react with both the first and secondmonomeric components. The crosslinking component is present in thecopolymers in an amount effective to facilitate returning a deformed IOLmade from the composition to its original shape, for example, in areasonable period of time, following insertion of a folded IOL in theeye.

It is to be understood by those of ordinary skill that the first, secondand third monomeric components should be such as to provide a copolymerthat is compatible for use in the eye, is optically clear and isotherwise suitable for use as an IOL material. It is also understoodthat each monomeric component includes at least one polymerizablefunctional group containing a carbon-carbon double bond.

The monomeric components, particularly if they have an aromatic moietycan be non-substituted or substituted. The substituents can include oneor more elements, such as oxygen, nitrogen, carbon, hydrogen, halogen,sulfur, phosphorus, and the like and mixtures and combinations thereof.

Particularly useful first monomeric components include styrene, vinylcarbazole, vinyl naphthalene, benzyl acrylate, phenyl acrylate, naphthylacrylate, pentabromophenyl acrylate, 2-phenoxyethyl acrylate,2-phenoxyethyl methacrylate, 2,3-dibromopropyl acrylate and any onemixture thereof.

In one embodiment, the first monomeric component is characterized asincluding one or more aryl-containing groups, which is believed toprovide the copolymer with a relative high refractive index. Theselection of an appropriate first monomeric component, and the amount ofsuch component used to form the copolymer, can effectively control therefractive index of the copolymer. Accordingly, it is not necessary forthe other monomeric components to appreciably contribute to the highrefractive index of the materials. This “single refractive indexcontrol” is very effective in achieving high refractive indexcopolymers, and allows flexibility in selecting the other monomericcomponent or components so that copolymers with advantageous properties,other than refractive index, for example, copolymers formable into IOLswhich can be effectively deformed (for insertion) at room temperature,can be obtained.

Particularly useful second monomeric components include n-butylacrylate, n-hexyl acrylate, 2-ethylhexyl acrylate, 2-ethoxyethylacrylate, 2,3-dibromopropyl acrylate, n-1,1-dihydroperfluorobutylacrylate and mixtures thereof.

The crosslinking monomeric component is often present in a minor amountrelative to the amounts of the first and second monomeric components.Typically, the crosslinking component is present in the copolymer in anamount of less than about 1% by weight of the copolymer. Thecrosslinking monomeric component is often selected from multifunctionalcrosslink component, preferably able to chemically react with at leastone functional group of each of the first monomeric component and thesecond monomeric component. The crosslinking monomeric component ischosen to have a reactivity ratio similar to both the first monomericcomponent and the second monomeric component. Examples of usefulcrosslinking monomeric components include ethylene glycoldimethacrylate, propylene glycol dimethacrylate, ethylene glycoldiacrylate and the like and any one mixture thereof.

In some of the more preferred embodiments, the first monomeric componentis of formula (I)

wherein: X is H or CH₃; m is 0-6; Y is nothing, O, S, or NR with R is H,C₁₋₄alkyl, iso-OC₃H₇, phenyl or benzyl;

Ar is any aromatic ring, such as benzene, which can be unsubstituted orsubstituted, including CH₃, C₁₋₄alkyl, C₁₋₃oxyalkyl, phenyl and benzyl.The aromatic substituents also include the aromatic substituents listedwith formula (I) above.

Suitable monomers of formula II include 2-ethylphenoxy acrylate,2-ethylphenoxy acrylate, 2-ethylthiophenyl acrylate, 2-ethylthiophenylacrylate, 3-phenylpropyl acrylate, 2-ethylaminophenyl acrylate, phenylacrylate, benzyl acrylate, 2-phenylethyl acrylate, 4-phenylbutylcrylate, 4-methylphenyl acrylate, 4-methylbenzyl acrylate,2-2-methylphenylethyl acrylate, 2-3-methylphenylethyl acrylate,2-4-methylphenylethyl acrylate, 2-(4-propylphenyl)ethyl acrylate,2-(4-(1-methylethyl)phenyl)ethyl acrylate, 2-(4-methoxyphenyl)ethylacrylate, 2-(4-cyclohexylphenyl)ethyl acrylate, 2-(2-chlorophenyl)ethylacrylate, 2-(3-chlorophenyl)ethyl acrylate, 2-(4-chlorophenyl)ethylacrylate, 2-(4-bromophenyl)ethyl acrylate, 2-(3-phenylphenyl)ethylacrylate, 2-(4-phenylphenyl)ethyl acrylate), 2-(4-benzylphenyl)ethylacrylate including for each listed the corresponding methacrylate.

It will be understood by those skilled in the art that among polymers ofacrylic esters, those made from acrylate ester monomers tend to havelower glass transition temperatures and to be more flexible thanpolymers of methacrylate esters. Accordingly, the arylacrylate/methacrylate copolymers used in the IOL's of this inventionwill generally comprise a greater mole percent of acrylate esterresidues than of methacrylate ester residues. It is preferred that thearyl acrylate monomers constitute from about 60 mole percent to about 95mole percent of the polymer, while the aryl methacrylate monomersconstitute from about 5 mole percent to about 40 mole percent of thepolymer.

The appropriate selection of monomeric components and their respectiveamounts in the copolymer should provide a polymeric material having aglass transition temperature not greater than about 60° C., preferablynot greater than 40° C. It is preferred to use polymers having a glasstransition temperature somewhat below normal body temperature and nogreater than normal room temperature, e.g., about 20° C. to 25° C., inorder that the lenses can be rolled or folded conveniently at roomtemperature.

One preferred copolymer material for an IOL comprises about 60-70 molepercent 2-phenylethyl acrylate (PEA); and about 30-40 mole percent2-phenylethyl methacrylate (PEMA). A homopolymer of the PEA has anoptical refractive index of about 1.56, and are relatively rigid. Forexample, while a one centimeter diameter rod of such a homopolymer issomewhat rubbery, if this rod is bent into a U-shape cracks will likelyform at the base of the U. A homopolymer of PEMA has a glass transitiontemperature of −58° C. The resulting copolymer has a refractive index of1.537. A one centimeter diameter rod of this copolymer can be folded180° with no observed cracking and return to its original shape within afew seconds.

The following hydrophobic acrylic formulation is blended, purged withnitrogen for 3 minutes and cured into a crosslinked copolymer.

-   -   89 wt. % 2-phenoxyethyl acrylate,    -   9.5 wt. % n-hexyl acrylate,    -   9.0 wt. % ethylene glycol dimethacrylate,    -   0.35 wt. % 2,2′-azobis(2,4-dimethylpentanenitrile),    -   0.05 wt. % 2,2′-azobis(2-methylbutanenitrile) and    -   1.5 wt. % x-monomer (need chemical name).

The cure temperature cycle used is as follows: heat from 250° C. to 500°C. in 30 minutes; maintain at 500° C. for 5 hours; heat from 500° C. to900° C. in 4 hours; maintain at 900° C. for 1 hour; and cool from 900°C. to 250° C. in 6 hours. The post-cure temperature cycle used is asfollows: heat from 250° C. to 1200° C. in 3 hours; maintain at 1200° C.for 2 hours; and cool from 1200° C. to 25° C. in 3 hours.

Another hydrophobic acrylic formulation is blended, purged with nitrogenfor 3 minutes and cured into a crosslinked copolymer. The cure andpost-cure heating and cooling regimens are the same as those describedabove.

-   -   88.5 wt. % 2-phenoxyethyl acrylate,    -   5 wt. % n-hexyl acrylate,    -   4 wt. % N-vinyl pyrrolidone    -   0.35.0 wt. % ethylene glycol dimethacrylate,    -   0.05 wt. % 2,2′-azobis(2,4-dimethylpentanenitrile),    -   0.05 wt. % 2,2′-azobis(2-methylbutanenitrile) and    -   1.5 wt. % x-monomer (see chemical structure below).

Another hydrophobic acrylic formulation is comprising 90 mole percent2-phenylethyl acrylate (PEA), 5 mole percent, 2-phenylethyl methacrylate(PEMA), 5 mole percent 1-6 hexanediol dimethacrylate (HDDMA), and 0.1percent by weight of bis-(4-t-butylcyclohexyl) peroxydicarbonate isdegassed and transferred into either an IOL mold and or a film mold madeof two glass plates with one layer of a polyethylene terephthalate filmon each facing side, with the plates being separated by a siliconegasket of 0.8 mm thickness. Both molds are designed so that there wouldbe no differential pressure buildup between the inside and the outsideof the mold during the polymerization. The mold is completely filled byinjecting the mixture, e.g., by means of a syringe, into a filling portuntil the mold was filled and excess monomer mixture was dischargedthrough an exit vent.

The filled molds are heated in an inert environment for 15 hours at 50°C. At the end of the polymerization period, the molds are opened and thecured intraocular lens and sheet of polymer are removed. The intraocularlens is observed to be soft, foldable, and of high refractive index(approximately 1.55) with a glass transition temperature ofapproximately 12° C.

Additional IOLs can be made using the above procedure but varying theproportions of the monomeric components. The formulations and glasstransition temperature (Tg) of the lenses are listed in Table 1.

TABLE 1 PEA PEMA POEA HDDMA BDDA Tg ° C. 88 10 — 2 — 10 78 20 — 2 — 1565 30 — — 3.2 17 80 15 — — 3.2 11 — 30 65 — 3.2 — BDDA isbutanedioldiacrylate crosslink agent POEA is 2-phenoxy acrylateLow Water Content Acrylic IOLs

The present invention relates to an acrylic IOL having a water contentfrom 5% to 15% by weight water in its equilibrated hydrated statewhereas many current hydrophobic acrylic IOLs on the market have anequilibrated hydrated water content of less than 4.5% by weight. Oneadvantage to the low water content acrylic IOLs is that one can observea reduction in the amount of water vacoule formation, often referred toin the art as ‘glistenings” while achieving particularly desirablephysical properties.

Like the hydrophobic acrylic IOL materials one typically would select afirst monomeric component, a second monomeric component and a third(crosslinking) component as previously described. The difference betweenthe two materials comes with the addition of a sufficient amount of afourth monomeric component. This fourth component is present in theacrylic polymer from about 2% to about 20% by weight. This fourthcomponent is generally referred to by those in the art as a hydrophilicmonomer. Also, the presence of hydrophilic monomer can often reduce thetackiness of the copolymer relative to a substantially identicalcopolymer without the fourth hydrophilic monomeric component. Inaddition, the presence of a hydrophilic monomeric component can help tominimize the formation of the described water vacuoles.

As used herein, the term “hydrophilic monomeric component” refers tocompounds which produce hydrogel-forming homopolymers, that is,homopolymers which in an equilibrated, hydrated state comprise at leastabout 20% by weight water based, and which physically swell as a resultof its water uptake. Specific examples of useful hydrophilic monomericcomponents include N-vinyl pyrrolidone; hydroxyalkyl acrylates andhydroxyalkyl methacrylates, such as 2-hydroxyethyl acrylate,2-hydroxyethyl methacrylate, 3-hydroxypropyl acrylate, 3-hydroxypropylmethacrylate, 4-hydroxybutyl acrylate, 4-hydroxybutyl methacrylate,2,3-dihydroxypropyl acrylate, 2,3-dihydroxypropyl methacrylate and thelike; acrylamide; N-alkyl acrylamides such as N-methyl acrylamide,N-ethyl acrylamide, N-propyl acrylamide, N-butyl acrylamide and thelike; acrylic acid; methacrylic acid; and the like and any one mixturethereof.

Alternatively, the fourth monomeric component is an aromatic-basedmonomer of formula IIG-D-Ar  (II)

wherein Ar is a C₆-C₁₄ aromatic group having at least a hydrophilicsubstituent, D is a divalent linking group, and G is a reactivefunctional group. In one embodiment, Ar is a phenyl or a fused aromaticring with a substituent selected from the group consisting of carboxy,alcohols (including monohydric and polyhydric alcohols), andcombinations thereof. Exemplary substituents on the aromatic groupinclude —COOH, —CH₂—CH₂OH, —(CHOH)₂—CH₂OH, —CH₂—CHOH—CH₂OH,poly(alkylene glycol) such as poly(ethylene glycol) having a formula of—(OCH₂CH₂)_(n)OH, wherein n is an integer from 1≦n≦20, and combinationsthereof.

In still another embodiment, Ar is a phenyl or a fused aromatic ringwith a substituent selected from the group consisting of carboxamide,dialkyl-substituted carboxamide, amino, alkanolamino, sulfonate,phosphonate, sulfate, phosphate, ureido, substituted sugars, andcombinations thereof.

G is a reactive functional group selected from the group consisting ofvinyl, allyl, acryloyl, acryloyloxy, methacryloyl, methacryloyloxy,epoxide, isocyanate, isothiocyanate, amino, hydroxyl, mercapto,anhydride, carboxylic, fumaryl, styryl, and combinations thereof.Preferably, G is selected from the group consisting of vinyl, styryl,acryloyloxy, and methacryloyloxy.

D is a divalent group selected from the group consisting of straight orbranched C₁-C₁₀ hydrocarbons, cyclic C₃-C₁₀ hydrocarbons, and alkyloxysubstituents. Preferably, D is a saturated straight C₁-C₁₀ hydrocarbondivalent group.

In one embodiment, an aromatic-based monomer has a formula (i)

wherein R is either hydrogen or CH₃.

In another embodiment, an aromatic-based monomer has a formula (ii)

wherein R is hydrogen or CH₃.

In still another embodiment, an aromatic-based monomer has a formula(iii)

wherein R¹ is —C(O)O—NH₂ or —C(O)—N(CH₃)₂.

Low water content acrylic IOLs were produced from formulations inn-hexanol based on the polymerization of the copolymer PPA/DMA/APDMS(3-phenylpropyl acrylate-co-N,N-dimethylacrylamide-co-3acryloyloxypropyldiphenylmethylsilane) in 20 w/v. % hexanol with thelisted amount of crosslink agent, ethyleneglycol dimethacrylate, setforth below in Table 2. All formulations contain 0.5 percent by weightIrgacure™ 819 (Ciba-Geigy, Basel, Switzerland) and no UV blocker. Thephysical and mechanical properties of each of the acrylic materials arealso reported.

Alternatively, the fourth monomeric component is an aromatic-basedmonomer of formula IIIG-D-Ar  (III)

wherein Ar is a substituted or non-substituted C₆-C₁₄ aromatic group, Dis a divalent, hydrophilic linking group, and G is a reactive functionalgroup. In one embodiment, Ar is a phenyl or a fused aromatic ring. Thelinking group D includes one or more substituent selected from the groupconsisting of carboxy, alcohols (including monohydric and polyhydricalcohols), and combinations thereof. Exemplary substituents on theinclude —COOH, —CH₂—CH₂OH, —(CHOH)₂—CH₂OH, —CH₂—CHOH—CH₂OH,poly(alkylene glycol) such as poly(ethylene glycol) having a formula of—(OCH₂CH₂)_(n)O—, wherein n is an integer from 1≦n≦20, and combinationsthereof.

In one embodiment, a monomer of formula (III) is represented as follows

wherein R is either hydrogen or CH₃, R¹ is hydrogen, C₃-C₁₂ alkyl withoptional oxygen functionality such as carboxy and alcohols (includingmonohydric and polyhydric alcohols).

TABLE 2 Formulation Mod Tear % wt. % (wt. %) R.I. (g/mm²) (g/mm) Elong.H₂O (75/25/0, 20/1) 1.5349 5.1 (75/25/0, 20/2) 1.5364 55 24 197 6.5(75/25/0, 20/3) 5.0 (65/25/10, 20/2) 1.5442 81 54 228 5 (65/25/10, 20/3)1.5448 143 57 178 5.7 (55/25/20, 20/1) 1.5409 94 79 332 5.5 (55/25/20,20/2) 1.5429 141 77 232 4.8 (55/25/20, 20/3) 1.5422 196 83 184 5

Low water content acrylic IOLs were produced from formulations inn-hexanol based on the polymerization of the copolymer PPA/DMA/MMA or(3-phenylpropyl acrylate-co-N,N-dimethylacrylamide-co-methylmethacrylate) set forth below in Table 3. All formulations contain acrosslink agent, ethyleneglycol dimethacrylate, at 3.0 wt. %, 0.5 wt. %Irgacure™ 819 (Ciba-Geigy, Basel, Switzerland) and no UV blocker. Thephysical and mechanical properties of each of the acrylic materials arealso reported.

TABLE 3 Mod Tear % % Formulation R.I. (g/mm²) (g/mm) Elong. H₂O 65/30/351.5108 290 127 254 11.3 65/0/35 1.5252 81 16 89 6.7 6510/35 1.5164 93 36137 10.1 6520/35 1.517  161 72 183 10.5Hydrophobic Silicone IOLs

The hydrophobic IOLs can be prepared from a reinforced cross-linkedsilicone prepolymer which includes a polymer containing 12 to 18 molpercent of aryl substituted siloxane units of the formula R⁴R⁵—SiO. Inthe formula, R⁴ and R⁵ are the same or different and represent phenyl,mono-lower alkyl substituted phenyl groups, or di-lower alkylsubstituted phenyl groups. Preferably both R4 and R5 are phenyl.

The silicone prepolymer can have end blockers containing siloxane unitsof the formula R¹R²R³—SiO₅ wherein R¹ and R² are alkyl, aryl orsubstituted alkyl or substituted aryl groups, and R¹ and R² can be thesame or different. The R³ group of the end blocking siloxane units is analkenyl group. Preferably, the end blocker is a dimethylvinyl siloxaneunit or a methacrylate. The balance of the silicone IOL can comprisedialkyl siloxane units of the formula R⁶R⁷—SiO wherein R⁶ and R⁷ are thesame or different from and are methyl or ethyl groups, and the elastomerhas a degree of polymerization from 100 to 2000. Preferably, R⁶ and R⁷are both methyl, and the degree of polymerization is approximately 250.

A trimethyl silyl treated silica reinforcer finely dispersed in theelastomer, present in a weight ratio of approximately 15 to 45 parts ofthe reinforcer to 100 parts of the silicone prepolymer, to provide alens material with a sufficient modulus value suitable for an IOL.Preferably, there is approximately 27 parts of reinforcer to 100 partsof the prepolymer.

In one embodiment, the hydrophobic silicone IOL is a silicone materialdescribed in U.S. Pat. No. 5,236,970. In another embodiment, A siliconeprepolymer that ie either monofunctional or difunctional can be used incombination with hydrophobic acrylic monomers. Such materials aredescribed in U.S. Pat. Nos. 7,169,874; 7,009,023; 6,908,978, each ofwhich is assigned to Bausch & Lomb Incorporated, Rochester, N.Y.

The lenses must exhibit sufficient strength to allow them to be foldedwithout fracturing. Polymers exhibiting an elongation of at least 150%are preferred. Most preferably, the polymers exhibit an elongation of atleast 200%. Lenses made from polymers which break at less than 150%elongation may not endure the distortion which necessarily occurs whenthey are rolled or folded to a dimension small enough to pass through asmall incision.

The copolymers are produced using conventional polymerizationtechniques. For example, the monomers can be blended together and heatedto an elevated temperature to facilitate the polymerization reaction.Catalysts and/or initiators, for example, selected from materials wellknown for such use in the polymerization art, may be included in themonomer mix in order to promote, and/or increase the rate of, thepolymerization reaction. Examples of such initiators include2,2′-azobis(2,4-dimethylpentanenitrile),2,2′-azobis(2-methylpropanenitrile), 2,2′-azobis(2-methylbutanenitrile),platinum-based initiators, peroxides such as benzoyl peroxide, UVinitiators such as diethoxyacetophenone, and the like and mixturesthereof. In addition, effective amounts of ultraviolet light absorbingmonomeric components, such as functional benzotriazole and benzophenonederivatives, may be included in the precursor monomer mix. Such UV lightabsorbing monomeric components are polymerized into the final copolymerto provide the final copolymer with effective UV light absorbingproperties.

In one embodiment, the copolymers are produced by mixing together thefirst monomeric component and the second monomeric component (and thefourth monomeric component, if any). This mixture is well blended,deareated and heated at an elevated temperature for a sufficient periodof time to form a partially polymerized viscous liquid. The times andtemperatures used will of course depend in-part on the monomericcomponents selected and is within the skill of one of ordinary skill inthe art. To the viscous liquid is added the crosslinking monomericcomponent and catalyst and/or an initiator. Alternately, all themonomeric components and catalyst and/or initiator can be combined ormixed together.

The viscous liquid, or monomeric mixture, is well blended, deareated andpoured into a mold. The liquid or mixture is allowed to cure. Aftercuring (and post-curing), the mold is disassembled and the molded opticrecovered.

The following non-limiting examples illustrate certain aspects of thepresent invention.

Example 1

To 65 parts of 3-phenylpropyl acrylate (PPA) was added 25 parts ofN,N-dimethylacrylamide (DMA), 20 parts of hexanol, 10 parts of methylmethacrylate (MMA), 3 parts of ethyleneglycol dimethacrylate (EG) ascrosslinker, 0.5% by weight Irgacure®819 as UV photoinitator and 0.25 wt% of a commercial triazole UV blocker (PQ 15014 from Aldrich Chemical).The clear solution was sandwiched between two silyated glass platesusing metal gaskets and exposed to visible light for 2 hours. Theresultant film (about 0.15 mm in thickness) was released from the platesand extracted in isopropanol (IPA) for 4 hours. The extracted film wasair-dried and then vacuum dried at ambient temperature (30 mm Hg) toremove any remaining IPA. Two discs were cut from the film. One disc wasplaced in borate buffered saline (BBS) and autoclaved (Market ForgeSterilmatic) within 30 minutes after contact with the BBS, and heatsterilized for 30 minutes at 122° C. and 15 psi. The heat sterilizeddisc slowly cooled to ambient temperature and stored in the BBS. Nodisc-like features (opaque discs) or vacuoles were observed followingsterilization or up to two weeks following sterilization.

The Example 1 process was repeated and provided near identicalresults—no disc-like features or vacuoles.

Comparative Example 1A (CE 1A)

The remaining disc from Example 1 was placed in the BBS for at least 15hours (overnight). The hydrated disc was autoclaved for 30 minutes at122° C. and 15 psi, and allowed to cool slowly to ambient temperature.Disc-like features were observed throughout the disc.

Comparative Example 1B (CE 1B)

The disc free of disc-like features or vacuoles was placed in BBS fortwo weeks and the autoclave step was repeated. Disc-like features wereobserved throughout the disc.

Examples 2 to 4

The same procedure described in Example 1 was used to make polymer filmsprepared from the polymer mixtures listed in Table 4A. Four discs werecut from each of the prepared polymer films. Two of the four discs wereautoclaved within 30 minutes of contact with the BBS. The clarity ofeach of the discs is reported in Table 4B.

TABLE 4A Example No. PPA DMA MMA EG 2 65 35 — 3 3 65 35 20 3 4 65 35 303

TABLE 4B Example No. stress features vacuoles 2 none none 3 two none 4two none

Comparative Examples 2 to 4

The remaining two discs from each of Examples 2 to 4 was placed in theBBS for at least 48 hours. The hydrated discs were autoclaved for 30minutes and allowed to cool slowly to ambient temperature. The clarityof each of the discs is reported in Table 4C.

TABLE 4C Example No. stress features vacuoles CE 2 TNC yes CE 3 TNC yesCE 4 TNC yes TNC—to numerous to count

Examples 5 to 7

The same procedure described in Example 1 was used to make polymer filmsprepared from the polymer mixtures listed in Table 5A. These films donot include methyl methacrylate and are polymerixed with 0.25 wt. % UVblocker and 0.25 wt. % Irgacure®369. Four discs were cut from each ofthe prepared polymer films. One disc for each Example (i.e., Disc 5a, 6aand 7a) was heat sterilized following a one hour hydration time in BBS.Another disc for each Example (i.e., Disc 5b, 6b and 7b) was heatsterilized following a four hour hydration time in BBS. Another disc foreach Example (i.e., Disc 5c, 6c and 7c) was heat sterilized following asix hour hydration time in BBS. Lastly, the fourth disc from eachExample (i.e., Disc 5 CE, 6 CE and 7 CE) was heat sterilized followingstorage in BBS overnight (about 14 hours). Disc 5 CE, 6 CE and 7 CE arecomparative examples and noted with CE. The clarity of each of the discsis reported in Tables 5B, 5C and 5D.

TABLE 5A Example No. PPA DMA EG 5 65 35 3 6 65 35 4 7 65 35 5

TABLE 5B Example No. stress features vacuoles 5a none none 5b none none5c few some 5 CE numerous numerous

TABLE 5C Example No. stress features vacuoles 6a none none 6b none none6c none many (center of disc) 6 CE numerous numerous

TABLE 5D Example No. stress features vacuoles 7a none none 7b none none7c none none 7 CE numerous numerous

1. A process for sterilizing an intraocular lens, the process comprising: providing a hydrophobic acrylic, or low water acrylic, intraocular lens and positioning the acrylic lens in a lens enclosure with an aqueous solution; and heating the lens enclosure to a temperature sufficient for sterilization, wherein the heating of the lens enclosure must begin before the acrylic lens reaches an equilibrated, hydrated state following contact of the lens with the aqueous solution, said sterilized intraocular lens to have less than sixty percent of total volume of disc-like features after 60 days following sterilization compared to an acrylic lens of the same composition that was sterilized under the same conditions, but in an equilibrated, hydrated state.
 2. The process of claim 1 wherein the acrylic lens comprises acrylate or methacrylate monomeric units with aromatic functionality.
 3. The process of claim 1 wherein the intraocular lens comprises silicon monomeric units.
 4. The process of claim 1 further comprising extracting the acrylic intraocular lens with a low-expanding organic solvent to remove unwanted polymerization products or non-reacted monomer from the polymerized lens, and drying the solvent-extracted lens under vacuum at temperatures from 40° C. to 110° C. for at least thirty minutes prior to positioning the acrylic lens in a lens enclosure.
 5. The method of claim 1 wherein the providing of the acrylic intraocular lens includes drying a solvent-extracted lens under vacuum at temperatures from 40° C. to 110° C. for at least thirty minutes.
 6. The method of claim 1 wherein said sterilized intraocular lens has less than thirty percent of total volume of disc-like features after 60 days following sterilization compared to the lens of the same composition that was sterilized under the same conditions, but in an equilibrated, hydrated form.
 7. The method of claim 1 further comprising sealing the lens enclosure prior to heating.
 8. The method of claim 1 wherein the heating of the lens enclosure begins within two hours of contacting the acrylic lens with the aqueous solution with the lens package at room temperature.
 9. The method of claim 1 wherein the acrylic lens comprises acrylate or methacrylate monomeric units of formula III

wherein R is either hydrogen or CH₃, R¹ is hydrogen, C₃-C₁₂ alkyl with optional oxygen functionality selected from carboxy and monohydric or polyhydric alcohols.
 10. The method of claim 1 wherein the acrylic lens is a copolymer comprising: a first monomeric component, present in the copolymer from 30% to 85% by weight, a homopolymer of the first monomeric component will have a refractive index of at least about 1.50; and a second monomeric component, present in the copolymer from 5% to about 30% by weight, a homopolymer of the second monomeric component will have a glass transition temperature from about −100° C. to about 60° C., wherein the first and the second monomeric components comprise at least about 80% by weight of the copolymer. 